Solidified deposits may develop in hollow organs or ducts within humans and animals and cause numerous health problems, as is known to those skilled in the art. Such deposits include cholesterol-rich gallstones. biliary duct stones in the biliary tract, and cholesterol plaque in the vascular system, for example. These deposits may be removed from the body in various ways, the most common being surgery, particularly in the case of gallstones.
Gallstones are solidified deposits or calculi composed of cholesterol, bilirubin, bilirubin complexes and other components derived from bile. A majority of gallstones have a high cholesterol content distributed through their mass and therefore lend themselves to in vivo dissolution by introduction of a cholesterol dissolving solvent or cosolvent mixture into the area of the body where the calculi are located. In vivo dissolution avoids many of the hazards and complications of surgery, and so is desireable when it can be performed. It has been found to be advantageous, furthermore, to perform the dissolution by repeatedly oscillating or agitating the solvent around the calculi to enhance the dissolution rate. In addition, in the case of gallstones in the gallbladder, it is helpful to withdraw the immiscible bile-solvent mixture periodically in order to renew the cholesterol-bearing solvent and improve stone contact, thus enhancing the dissolution process. This dissolution process is described in U.S. Pat. No. 4,655,744, and apparatus for accomplishing it is described in U.S. Pat. No. 4,723,941, both of which are incorporated by reference fully herein.
However, in order for in vivo dissolution of cholesterol-rich calculi to be functional, effective solvents must be located and used. This is a difficult matter, and numerous researchers have evaluated solvents, largely unsuccessfully, for such purposes over the past few years. Large numbers of solvents have been tried, and only three are commonly recognized as particularly effective: diethyl ether, monooctanoin, and methyl tertiary-butyl ether ("MtBE"). Monooctanoin, according to the literature, dissolves between about 12 to 23 grams of cholesterol per deciliter of solvent at 37.degree. C.; our measurements (some are set forth later) indicate that MtBE dissolves about 24 grams of cholesterol per deciliter of solvent at 30.degree. C., and that diethyl ether dissolves about 27 grams of cholesterol per deciliter solvent at 30.degree. C.
Each, however, does present certain problems associated with its use. For example, diethyl ether's normal boiling point, 34.6.degree. C., is so low that it converts into a gas when introduced into the body for dissolution, and it is very flammable. Monooctanoin, on the other hand, has such a high viscosity that dissolution occurs very slowly, taking days or weeks to accomplish in vivo. MtBE, on the other hand, is fairly effective, dissolution sometimes being accomplishable in a day, but it is highly flammable so that a great deal of care must be exercised when purifying and using it. Further, because MtBE is immiscible with bile and has a lower density than bile, and because gallstones have a higher density than bile, MtBE floats on bile-encompassed gallstones, thus making solvent-gallstone contact difficult, particularly without agitation or mixing.
It would be desireable to develop a broader group of solvents usable for such dissolution processes which avoid at least some of the difficulties associated with the solvents now known to be effective.